Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Iejimalide C Is a Potent V-ATPase Inhibitor, and Induces Actin Disorganization
Sayaka KazamiMasak TakaineHiroyasu ItohTakaaki KubotaJun’ichi KobayashiTakeo Usui
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2014 Volume 37 Issue 12 Pages 1944-1947


Iejimalides (IEJLs) A–D are 24-membered macrolides isolated from a tunicate Eudistoma cf. rigida, and exhibit potent cytotoxicity in vitro and antitumor activity in vivo. We previously reported that the molecular target of IEJL-A and -B was the vacuolar-type H+-ATPases (V-ATPases). However IEJL-C and -D, which are sulfonylated IEJL-A and -B, respectively, show more potent antitumor activity, and their molecular targets remain to be discovered. Here, we report that IEJL-C is also a potent V-ATPase inhibitor by binding in a site similar to the bafilomycin-binding site. Two-hour treatment with IEJL-C resulted in the complete disappearance of acidic organelles in HeLa cells. Interestingly, after 24-h treatment, small actin aggregates were observed instead of actin fibers. The same actin reorganization was also observed in cells treated with another V-ATPase inhibitor, bafilomycin A1. Because IEJLs did not inhibit actin polymerization in vitro, these results suggest that the primary target of IEJL-C, as well as IEJL-A and -B, is V-ATPase, and actin reorganizations are probably caused by the disruption of pH homeostasis via V-ATPase inhibition.

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© 2014 The Pharmaceutical Society of Japan
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